Pharmacological inhibition of Dock5 prevents osteolysis by affecting osteoclast podosome organization while preserving bone formation.
Osteoporosis is caused by excessive activity of bone-degrading osteoclasts over bone-forming osteoblast. Standard antiosteolytic treatments inhibit bone resorption by inducing osteoclast loss, with the adverse effect of hindering also bone formation. Formation of the osteoclast sealing zone requires Dock5, a guanine nucleotide exchange factor for the small GTPase Rac, and C21, a chemical inhibitor of Dock5, decreases bone resorption by cultured osteoclasts. Here we show that C21 directly inhibits the exchange activity of Dock5 and disrupts osteoclast podosome organization. Remarkably, C21 administration protects mice against bone degradation in models recapitulating major osteolytic diseases: menopause, rheumatoid arthritis and bone metastasis. Furthermore, C21 administration does not affect bone formation and is not toxic. Our results validate the pharmacological inhibition of Dock5 as a novel therapeutic route for fighting osteolytic diseases while preserving bone formation.


Methods for counting residual leukocytes in leukocyte-depleted plasma-a comparison between a routine hematology instrument, the Nageotte chamber, flow cytometry, and a fluorescent microscopy analyzer.
Counting very low levels of leukocytes is technically challenging but mandatory for quality control of leukocyte-depleted plasma. Established assays, such as flow cytometry and counting in the Nageotte chamber, are laborious and expensive. The aim of this study was to test two alternative assays, the cerebrospinal fluid program in the routine hematology analyzer ADVIA 2120 and a fluorescence microscopy analyzer, the ADAM-rWBC. Linearity, accuracy, and precision were established for the ADVIA 2120, the ADAM-rWBC analyzer and the Nageotte chamber with flow cytometry as the reference method. Two hundred consecutive leukocyte-depleted donor plasma samples were also tested. The ADAM-rWBC analyzer and the Nageotte chamber fulfilled all quality requirements. Flow cytometry fulfilled the requirements for linearity and precision. The ADVIA 2120 analyzer did not fully reach the quality criteria, and flow cytometry did not reach quality criteria on accuracy. No false-positive results on donor plasma samples were recorded. The ADAM-rWBC is suitable for the purpose of quality control of residual leukocytes in leukocyte-depleted plasma. For the ADVIA 2120, further improvements and studies are needed to reach the quality requirements stated in this study.


Effects of keto analogues of essential amino acids in portal-systemic encephalopathy.
Keto analogues of five essential amino acids (valine, leucine, isoleucine, methionine, and phenylalanine) were given either parenterally or orally in varying proportions to 11 patients with portal-systemic encephalopathy and hyperammonemia. Plasma concentrations of amino acids corresponding to the infused analogues, including alloisoleucine, increased significantly after infusions. Plasma tyrosine and glycine, which were abnormally elevated in control samples, fell after the infusions. After one to five daily infusions, the ratio of essential to nonessential amino acids in fasting plasma was increased toward normal, suggesting improved protein nutrition. Arterial blood ammonia and glutamate did not change immediately after infusions, but a pronounced decrease in glutamine (42%) was observed. Eight nitrogen balance studies performed in 5 patients during 3 to 12 days of oral or intravenous keto acid therapy failed to show consistent improvement in balance as compared with control periods. After five courses of oral therapy there was again significant improvement in the ratio of essential to nonessential amino acids. No toxicity from keto analogue administration was found, and clinical improvement, as assessed by mental status and psychological testing occurred in 8 of 11 patients. These studies suggest keto analogues of essential amino acids are converted to the corresponding amino acids in patients with portal-systemic encephalopathy, and that such therapy may be of benefit.


Sex-specific comparison of clinical characteristics and prognosis in Crohn's disease: A retrospective cohort study of 611 patients in China.
Background: Real-world data on the impact of sex on the disease progression and prognosis of Crohn's disease (CD) from large-scale Chinese cohorts are lacking. Aims: This study aimed to evaluate sex disparities in the clinical characteristics of, disease progression behaviours of and surgery-related risk factors for CD. Methods: A retrospective cohort study comprising 611 patients consecutively diagnosed with CD at Peking Union Medical College Hospital from January 2000 to December 2020 was conducted. Multivariate Cox regression and survival analyses was performed to assess the risk factors for disease progression and CD-related surgery in sex subgroups. Results: Male sex was an independent protective factor against multisystemic extraintestinal manifestations [EIMs] (HR: 0.52, p = 0.03) and a risk factor for intestinal perforation (HR: 1.85, p = 0.01). Male patients had longer EIM-free survival (p = 0.024) and shorter intestinal perforation-free survival (PFS) than females (p = 0.012). Of the 397 patients with the A2 classification, male patients had a higher risk of CD-related surgery (HR: 1.80, p = 0.028) and shorter surgery-free survival (SFS) than female patients (p = 0.04). Conclusion: Sex disparities in disease progression and outcomes of CD were revealed in a single Chinese centre. Male sex was independently associated with worse disease progression and prognosis including multisystemic EIMs and perforation, which suggests the need for individualized management according to risk classification.


Energy metabolism in the normal and failing heart: potential for therapeutic interventions.
The chronically failing heart has been shown to be metabolically abnormal, in both animal models and in patients. Little data are available on the rate of myocardial glucose, lactate and fatty acid metabolism and oxidation in heart failure patients, thus at present, it is not possible to draw definitive conclusions about cardiac substrate preference in the various stages and manifestations of the disease. Normal cardiac function is dependent on a constant resynthesis of ATP by oxidative phosphorylation in the mitochondria. The healthy heart gets 60-90% of its energy for oxidative phosphorylation from fatty acid oxidation, with the balance from lactate and glucose. There is some indication that compensated NYHA Class III heart failure patients have a significantly greater rate of lipid oxidation, and decreased glucose uptake and carbohydrate oxidation compared to healthy age-matched individuals, and that therapies that acutely switch the substrate of the heart away from fatty acids result in improvement in left ventricular function. Clinical studies using long-term therapy with beta-adrenergic receptor antagonists show improved left ventricular function that corresponds with a switch away from fatty acid oxidation towards more carbohydrate oxidation by the heart. These findings suggest that chronic manipulation of myocardial substrate oxidation toward greater carbohydrate oxidation and less fatty acid oxidation may improve ventricular performance and slow the progression of left ventricular dysfunction in heart failure patients. At present, this intriguing hypothesis requires further evaluation.


The lactate-dependent enhancement of hydroxyl radical generation by the Fenton reaction.
The effect of lactic acid (lactate) on Fenton based hydroxyl radical (*OH) production was studied by spin trapping, ESR, and fluorescence methods using DMPO and coumarin-3-carboxylic acid (3-CCA) as the *OH traps respectively. The *OH adduct formation was inhibited by lactate up to 0.4 mM (lactate/iron stoichiometry = 2) in both experiments, but markedly enhanced with increasing concentrations of lactate above this critical concentration. When the H2O2 dependence was examined, the DMPO-OH signal was increased linearly with H2O2 concentration up to 1 mM and then saturated in the absence of lactate. In the presence of lactate, however, the DMPO-OH signal was increased further with higher H2O2 concentration than 1 mM, and the saturation level was also increased dependent on lactate concentration. Spectroscopic studies revealed that lactate forms a stable colored complex with Fe3+ at lactate/Fe3+ stoichiometry of 2, and the complex formation was strictly related to the DMPO-OH formation. The complex formation did not promote the H2O2 mediated Fe3+ reduction. When the Fe3+ -lactate (1:2) complex was reacted with H2O2, the initial rate of hydroxylated 3-CCA formation was linearly increased with H2O2 concentrations. All the data obtained in the present experiments suggested that the Fe3+-lactate (1:2) complex formed in the Fenton reaction system reacts directly with H2O2 to produce additional *OH in the Fenton reaction by other mechanisms than lactate or lactate/Fe3+ mediated promotion of Fe3+/Fe2+ redox cycling.


The association of clinical conditions and serologic tests with CD4+ lymphocyte counts in HIV-infected subjects without AIDS.
Early intervention guidelines in HIV infection require knowledge of CD4+ lymphocyte count; however, CD4+ determinations require special laboratory procedures and may not be readily available in all situations. Using data from 207 HIV-seropositive homosexual men without AIDS, we evaluated the association of difference clinical conditions or serologic tests with CD4+ count. Men with conditions including seborrheic dermatitis, hairy leukoplakia, oral candidiasis and chronic diarrhea, and men with beta2-microglobulin levels greater than or equal to 4.0 mg/l had significantly lower CD4+ counts. However, the probability that a subject with such parameters had less than 200 x 10(6)/l CD4+ cells was limited (25-63%). Although the probability that a subject with such parameters had less than 500 x 10(6)/l CD4+ cells was better (76-88%), the probability that a person without these parameters had greater than or equal to 500 x 10(6)/l CD4+ cells was only 45-50%. Clinical and serologic parameters may provide important prognostic information, but cannot be used to reliably determine the level of CD4+ cells.


[Symptoms, depression, and coping behaviors of university students].
The purpose of this study was to examine the relationship among subjective symptoms, depression, and stress coping behavior of university students. The survey was carried out on a convenience sample of 298 university students. The questionnaire consisted of each scale for symptoms, depression, and stress coping behaviors. Data analysis procedure included the factor analysis for stress coping behaviors, and the correlation analysis describing a relationship among symptoms, depression, and stress coping behaviors. There were significant correlations between depression and the three types of symptoms : general, psychological, and somatic symptom. Subjects using the negative-emotional-response coping and the self-control coping showed a more severe depression, and those using the problem-solving reappraisal coping and the positive-emotional-response coping showed a milder depression. Subjects using the negative-emotional-response coping complained of all 3 types of symptoms severely, and those using the positive-emotional-response coping complained of general symptoms mildly. Of five stress coping methods, the negative-emotional-response and the positive-emotional-response coping methods were related to both symptoms and depression significantly. This study suggests that the emotional-oriented coping method has more important role for university student's depression and their subjective symptoms than the problem-oriented coping or social supports seeking coping. Further study needs to be conducted to help students effective coping mechanism for good mental health. Also it is necessary for university students to recognize that their symptoms are associated with depression.


Mutational spectrum and phenotypic variability of Duchenne muscular dystrophy and related disorders in a Bangladeshi population.
Duchenne muscular dystrophy (DMD) is a severe rare neuromuscular disorder caused by mutations in the X-linked dystrophin gene. Several mutations have been identified, yet the full mutational spectrum, and their phenotypic consequences, will require genotyping across different populations. To this end, we undertook the first detailed genotype and phenotype characterization of DMD in the Bangladeshi population. We investigated the rare mutational and phenotypic spectrum of the DMD gene in 36 DMD-suspected Bangladeshi participants using an economically affordable diagnostic strategy involving initial screening for exonic deletions in the DMD gene via multiplex PCR, followed by testing PCR-negative patients for mutations using whole exome sequencing. The deletion mapping identified two critical DMD gene hotspot regions (near proximal and distal ends, spanning exons 8-17 and exons 45-53, respectively) that comprised 95% (21/22) of the deletions for this population cohort. From our exome analysis, we detected two novel pathogenic hemizygous mutations in exons 21 and 42 of the DMD gene, and novel pathogenic recessive and loss of function variants in four additional genes: SGCD, DYSF, COL6A3, and DOK7. Our phenotypic analysis showed that DMD suspected participants presented diverse phenotypes according to the location of the mutation and which gene was impacted. Our study provides ethnicity specific new insights into both clinical and genetic aspects of DMD.


Urinary morbidity and incontinence following transurethral resection of the prostate after brachytherapy.
We analyzed the risk of urinary morbidity and incontinence in patients undergoing transurethral resection of the prostate (TURP) following prostate brachytherapy. A total of 2,050 patients underwent transperineal radioactive seed implantation of the prostate with or without external beam radiation therapy for the diagnosis of prostate cancer between June 1990 and February 2004. Of the 2,050 patients 38 (2%) underwent minimal (channel) TURP due to urinary symptoms or retention. Urinary morbidity was recorded prior to implantation and at followup intervals using the International Prostate Symptom Score and quality of life assessment scores. All patients underwent post-implantation computerized tomography based dosimetry at 1 month. The dose to 90% of prostate volume, prostate volume covered by 15% of the prescription dose and dose to 30% or 5 cm of urethral volume were recorded. Of the 38 patients 11 (29%) underwent Pd implantation alone and 12 (32%) received a partial (67%) Pd implant with external beam radiation therapy to a median dose of 45 Gy (range 41.4 to 59.4), while 15 (39%) underwent I implantation alone. Median followup after implantation was 38 months (range 2 to 97). Seven of the 38 patients (18%) undergoing TURP had urinary incontinence. Median time to TURP was 11 months (range 1 to 73). 25% Of patients who received an implant and external beam radiotherapy had urinary incontinence following TURP compared with 15% who underwent implantation alone (p = 0.26). There was no significant correlation between incontinence risk based on the dose to 90% of prostate volume (p = 0.32), the dose to 30% or 5 cm of urethral volume (p = 0.30) or prostate volume covered by 15% of the prescription dose (p = 0.36). Two of 24 patients (8%) who had underwent 2 years or less after implantation had urinary incontinence compared with 5 of 14 (36%) who underwent TURP greater than 2 years following implantation (p = 0.04). Urinary incontinence developed in 18% of patients who underwent TURP following prostate brachytherapy. No significant correlations between radiation dose, preimplant prostate volume or hormonal therapy were identified with regard to this risk. Patients in late retention or with obstructive symptoms (greater than 2 years) following implantation who require TURP are at greater risk for incontinence.


Decentralized Control for Swarm Robots That Can Effectively Execute Spatially Distributed Tasks.
A swarm robotic system is a system in which multiple robots cooperate to fulfill a macroscopic function. Many swarm robots have been developed for various purposes. This study aims to design swarm robots capable of executing spatially distributed tasks effectively, which can be potentially used for tasks such as search-and-rescue operation and gathering scattered garbage in rooms. We propose a simple decentralized control scheme for swarm robots by extending our previously proposed non-reciprocal-interaction-based model. Each robot has an internal state, called its workload. Each robot first moves randomly to find a task, and when it does, its workload increases, and then it attracts its neighboring robots to ask for their help. We demonstrate, via simulations, that the proposed control scheme enables the robots to effectively execute multiple tasks in parallel under various environments. Fault tolerance of the proposed system is also demonstrated.


A sparse structure learning algorithm for Gaussian Bayesian Network identification from high-dimensional data.
Structure learning of Bayesian Networks (BNs) is an important topic in machine learning. Driven by modern applications in genetics and brain sciences, accurate and efficient learning of large-scale BN structures from high-dimensional data becomes a challenging problem. To tackle this challenge, we propose a Sparse Bayesian Network (SBN) structure learning algorithm that employs a novel formulation involving one L1-norm penalty term to impose sparsity and another penalty term to ensure that the learned BN is a Directed Acyclic Graph--a required property of BNs. Through both theoretical analysis and extensive experiments on 11 moderate and large benchmark networks with various sample sizes, we show that SBN leads to improved learning accuracy, scalability, and efficiency as compared with 10 existing popular BN learning algorithms. We apply SBN to a real-world application of brain connectivity modeling for Alzheimer's disease (AD) and reveal findings that could lead to advancements in AD research.


Parametric evaluation of heart rate variability during the menstrual cycle in young women.
Evaluation of heart rate variability (HRV) is based on analysis of consecutive R-R intervals and may provide quantitative information on the modulation of cardiac vagal and sympathetic efferent activities. In particular, power spectral analysis as well as the fractal dimension of HRV represent non-invasive measures that reflect brain-heart interaction in different physiopathological conditions. This study was performed to investigate the relationship between autonomic nervous cardiac influence and three phases (menses, follicular phase and luteal phase) of the menstrual cycle. Heart rate (HR) was recorded in 6 eumenorrheic young females, continuously for 20 min, at rest. From the tachograms, fractal dimension, FFT spectra and beta coefficient were evaluated. The components of two spectral bands were calculated: 0.040 Hz - 0.150 Hz (low frequency, LF), and 0.150 Hz - 0.80 Hz (high frequency, HF). The results indicate no correlation between HR and follicular as well as luteal phase of the menstrual cycle. Total power and HF spectral component increase, whereas LF spectral component decreases in the luteal phase compared to the follicular one. The fractal dimension does not show significant differences among the three phases. Beta coefficient decreases during luteal phase in respect of follicular one and menses. In conclusion, these results indicate in healthy young women a correlation between female sex hormones (17 beta-oestradiol, progesterone and pituitary gonadotrophins) concentrations and some HRV parameters with higher HR variability during the luteal phase.


Iron-Binding Catechols and Virulence in Escherichia coli.
Previous work suggested that virulent bacteria, which can grow rapidly in serum, must possess a specific mechanism for removing iron from its transferrin complex. Two strains of Escherichia coli were examined with this in mind. Strain O141, which showed inoculum-dependent growth in serum and multiplied in the mouse peritoneum, secreted iron-binding catechols into both synthetic medium and serum. One of these compounds has an association constant for iron similar to that of transferrin. Both transferrin and ethylenediamine-di-o-hydroxyphenyl acetic acid (EDDA), which have very high affinities for ferric iron, induced catechol synthesis in growing cultures of strain O111. This organism was inhibited by normal horse serum. Further work showed that traces of specific antibody inhibited catechol synthesis by O111 exposed to EDDA; therefore, the existence of this inhibitory process means that the organism can no longer obtain Fe(3+), which all remains bound to transferrin in serum. In vivo, the inhibition of O111 is similar to that produced by serum in vitro. Neither phagocytosis nor killing by complement appeared to be of any significance during the first 4 h of the infections. Significantly, the purified catechol was capable of abolishing bacteriostasis in vivo. Since these results show that the production of iron-binding catechols is essential for rapid bacterial growth both in vitro and in vivo, these compounds should therefore be considered as true virulence factors. Conversely, any interference by the host with the production or activity of these compounds would constitute an important aspect of antibacterial defense.


Polymyalgia rheumatica -- diagnosis and management.
Polymyalgia rheumatica (PMR) is a common inflammatory rheumatic disease and an indication for long term treatment with oral steroids. Its incidence rises progressively beyond the age of 50 years. For the most part, PMR is managed in primary care. This article highlights the main points in the British Society for Rheumatology and the British Health Professionals in Rheumatology guidelines that may be useful to general practitioners in the primary care setting. Different levels of awareness of the condition between practitioners, and a lack of uniform diagnostic criteria may impede correct diagnosis and management of PMR. Updated international guidelines produced by the British Society for Rheumatology and the British Health Professionals in Rheumatology can aid diagnosis and direct treatment and disease monitoring.


Ultrafast anisotropic dynamics of hyperbolic nanolight pulse propagation.
Polariton pulses-transient light-matter hybrid excitations-traveling through anisotropic media can lead to unusual optical phenomena in space and time. However, studying these pulses presents challenges with their anisotropic, ultrafast, and nanoscale field variations. Here, we demonstrate the creation, observation, and control of polariton pulses, with in-plane hyperbolic dispersion, on anisotropic crystal surfaces by using a time-resolved nanoimaging technique and our developed high-dimensional data processing. We capture and analyze movies of distinctive pulse spatiotemporal dynamics, including curved ultraslow energy flow trajectories, anisotropic dissipation, and dynamical misalignment between phase and group velocities. Our approach enables analysis of polariton pulses in the wave vector time domain, demonstrating a time-domain polaritonic topological transition from lenticular to hyperbolic dispersion contours and the ability to study the polariton-induced time-varying optical forces. Our findings promise to facilitate the study of diverse space-time phenomena at extreme scales and drive advances in ultrafast nanoimaging.


Androgen-induced myogenesis and chondrogenesis in the larynx of Xenopus laevis.
We investigated a possible role for testosterone-induced cell proliferation in the development of sexual dimorphism in the larynx of South African clawed frogs, Xenopus laevis. Androgen-induced cell proliferation was studied using [3H]thymidine autoradiography. Nuclei of cartilage, perichondrium, and muscle were labeled in the larynx of sexually immature frogs of both sexes but not in adults. Cell proliferation did not occur with estradiol treatment nor was it seen in nonlaryngeal muscle or cartilage. Electron microscopic/autoradiographic studies of laryngeal muscle indicate that testosterone stimulates satellite cell division which later results in formation of myonuclei. We conclude that testosterone induces both chondrogenesis and myogenesis in juvenile larynx and that this process may contribute to the pronounced sexual dimorphism of the adult vocal organ.


von Willebrand factor does not influence atherogenesis in arteries subjected to altered shear stress.
The role of von Willebrand factor (vWF) in arterial neointimal formation that develops in arteries with altered shear stress was investigated using normal, heterozygous, and homozygous von Willebrand disease pigs (ie, vWD, or lacking vWF) that were fed normal pig chow. Shear stress was applied to carotid and femoral arteries with a Goldblatt clamp for 14 days, producing a > or = 80% stenosis. Neointimal lesion size was measured by computer-assisted morphometry. Expression of proliferative cell nuclear antigen (PCNA) by neointimial and medial cells was used as a relative index of proliferative activity. For shear-stressed arteries, there was no significant difference in the number of smooth muscle cell layers in the lesion, lesion size, and percent of PCNA-positive neointimal or medial cells among normal, heterozygous, and homozygous vWD pigs (P> or =.1, ANOVA). Lesions in pigs that expressed vWF (normals and heterozygotes) contained large amounts of vWF in the neointima, whereas lesions in vWD pigs had no detectable vWF. Moreover, no foam cells were detected in the lesions. Thus, the absence of vWF apparently does not alter the size of lesions in shear-stressed arteries in vWD pigs or the number of neointimal or medial cells expressing PCNA. Mechanism(s) involved with shear-induced modulation of smooth muscle cell proliferation, then, can operate independently of vWF in normolipemic pigs.


Infant neurobehavior following prenatal exposure to methadone or buprenorphine: results from the neonatal intensive care unit network neurobehavioral scale.
This study examined the neurobehavioral functioning of neonates prenatally exposed to methadone (n = 11) or buprenorphine (n = 10), who underwent the Neonatal Intensive Care Unit Network Neurobehavioral Scale (NNNS) examinations on days 3, 5, 7, 10, and 14 post-delivery. Linear mixed model analyses revealed that NNNS scores of arousal and excitability showed significant differences between medications over time. Compared to neonates who did not require medication to treat neonatal abstinence syndrome (NAS), neonates receiving pharmacotherapy for NAS showed differences over time in quality of movement, excitability, and lethargy. Results suggest the NNNS may detect subtle differences over time between both neonates prenatally exposed to methadone or buprenorphine and neonates pharmacologically treated or untreated for NAS.


Intensity, frequency, duration, and volume of physical activity and its association with risk of depression in middle- and older-aged Chinese: Evidence from the China Health and Retirement Longitudinal Study, 2015.
The general benefit of physical activity (PA) to one's mental health has been widely acknowledged. Nevertheless, the specific type and amount of PA that associates with lower risk of depression in China awaits further investigation. The present study was conducted on middle- and older-aged Chinese population with two objectives: 1) to understand the patterns of PA; 2) to measure the associations between depression and PA at different levels from various aspects. Using data from the China Health and Retirement Longitudinal Study (CHARLS, 2015), we selected 9118 community residents aged 45 years and older. Depressive symptoms were measured by 10-item Center for Epidemiologic Studies (CES-D 10). Multivariate logistic regression model was performed to examine the association between risk of depression and PA from four aspects including intensity, frequency, duration, and volume. Spending 1-2 days/week (OR = 0.58, 95% CI: 0.36, 0.91), less than 30 minutes each time (OR = 0.66, 95% CI: 0.42, 1.03) or 150-299 min/week (OR = 0.49, 95% CI: 0.28, 0.87) on Moderate Physical Activity (MPA) was associated with lower odds of depression in women. Spending 3-5 days/week (OR = 1.98, 95% CI: 1.29, 3.05) or 6-7 days/week (OR = 1.50, 95% CI: 1.07, 2.11), 4 hours and longer each time (OR = 1.65, 95% CI: 1.18, 2.32), 300 min/week or longer (OR = 1.65, 95% CI: 1.22, 2.24) on Vigorous Physical Activity (VPA) in total, or 2250 Metabolic Equivalent of Task (OR = 1.73, 95% CI: 1.26, 2.38) on Moderate-to-Vigorous PA was associated with higher risk of depression in men. The association between depression and PA depended largely on intensity and gender. Lower frequency, shorter duration, and moderate amount of MPA was associated with lower risk of depression in women. Risk of depression was higher in men who spent higher frequency, longer duration, and overlong time on VPA.


Complementary and alternative medicine in predoctoral dental curricula: an exploratory survey of U.S. dental schools.
The purpose of this study was to identify the prevalence of complementary and alternative medicine (CAM) education in U.S. dental schools. A survey was administered via e-mail to each U.S. dental school's academic dean, and data were collected from respondents in a fillable PDF form submitted electronically to the study investigators. The survey asked respondents whether CAM was taught at the institution; if the response was yes, information was requested regarding the CAM therapies included, credentials of the instructor, number of hours taught, reason for teaching CAM, and format in which CAM was taught. Of the sixty dental schools contacted, twenty-two responded to the survey (37 percent response rate). Of these respondents, ten (45.5 percent) reported offering instruction in CAM as part of their predoctoral curricula. Herb/drug interactions were found to be taught with more frequency than any other CAM topic (in six out of the ten institutions). Limitations of the study are discussed, and suggestions for future studies are made.


Role of exchange and correlation in high-harmonic generation spectra of H2, N2, and CO2: Real-time time-dependent electronic-structure approaches.
This study arises from the attempt to answer the following question: how different descriptions of electronic exchange and correlation affect the high-harmonic generation (HHG) spectroscopy of H2, N2, and CO2 molecules? We compare HHG spectra for H2, N2, and CO2 with different ab initio electronic structure methods: real-time time-dependent configuration interaction and real-time time-dependent density functional theory (RT-TDDFT) using truncated basis sets composed of correlated wave functions expanded on Gaussian basis sets. In the framework of RT-TDDFT, we employ Perdew-Burke-Ernzerhof (PBE) and long-range corrected Perdew-Burke-Ernzerhof (LC-ωPBE) functionals. We study HHG spectroscopy by disentangling the effect of electronic exchange and correlation. We first analyze the electronic exchange alone, and in the case of RT-TDDFT with LC-ωPBE, we use ω = 0.3 and ω = 0.4 to tune the percentage of long-range Hartree-Fock exchange and short-range exchange PBE. Then, we added the correlation as described by the PBE functional. All the methods give very similar HHG spectra, and they seem not to be particularly sensitive to the different description of exchange and correlation or to the correct asymptotic behavior of the Coulomb potential. Despite this general trend, some differences are found in the region connecting the cutoff and the background. Here, the harmonics can be resolved with different accuracy depending on the theoretical schemes used. We believe that the investigation of the molecular continuum and its coupling with strong fields merits further theoretical investigations in the near future.


Comparison Between Pre-Log and Post-Log Statistical Models in Ultra-Low-Dose CT Reconstruction.
X-ray detectors in clinical computed tomography (CT) usually operate in current-integrating mode. Their complicated signal statistics often lead to intractable likelihood functions for practical use in model-based image reconstruction (MBIR). It is therefore desirable to design simplified statistical models without losing the essential factors. Depending on whether the CT transmission data are logarithmically transformed, pre-log and post-log models are two major categories of choices in CT MBIR. Both being approximations, it remains an open question whether one model can notably improve image quality over the other on real scanners. In this study, we develop and compare several pre-log and post-log MBIR algorithms under a unified framework. Their reconstruction accuracy based on simulation and clinical datasets are evaluated. The results show that pre-log MBIR can achieve notably better quantitative accuracy than post-log MBIR in ultra-low-dose CT, although in less extreme cases, post-log MBIR with handcrafted pre-processing remains a competitive alternative. Pre-log MBIR could play a growing role in emerging ultra-low-dose CT applications.


Factors which influence physicians to join labor unions.
As members of a fiercely independent and individualistic profession, physicians have historically resisted the lure of organizing into collectives and have steadfastly maintained their autonomy. With the advent of managed care, the conditions of work have been altered and many of the assumptions guiding unions and collective bargaining have taken on renewed interest. Proponents of organizing physicians argue that unions can act as representative agents for health care providers to negotiate effectively with managed care organizations (MCO), insurance companies and government for conditions of work to help make their practice of medicine better for patients. Many physicians who previously rejected the notion of unions have reconsidered their entrenched positions and are beginning to weigh the costs and benefits associated with union membership.


Encoding, rehearsal, and recall in signers and speakers: shared network but differential engagement.
Short-term memory (STM), or the ability to hold verbal information in mind for a few seconds, is known to rely on the integrity of a frontoparietal network of areas. Here, we used functional magnetic resonance imaging to ask whether a similar network is engaged when verbal information is conveyed through a visuospatial language, American Sign Language, rather than speech. Deaf native signers and hearing native English speakers performed a verbal recall task, where they had to first encode a list of letters in memory, maintain it for a few seconds, and finally recall it in the order presented. The frontoparietal network described to mediate STM in speakers was also observed in signers, with its recruitment appearing independent of the modality of the language. This finding supports the view that signed and spoken STM rely on similar mechanisms. However, deaf signers and hearing speakers differentially engaged key structures of the frontoparietal network as the stages of STM unfold. In particular, deaf signers relied to a greater extent than hearing speakers on passive memory storage areas during encoding and maintenance, but on executive process areas during recall. This work opens new avenues for understanding similarities and differences in STM performance in signers and speakers.


The Impact of the Disease Trend on the Macro and Micro-Nutrients Intake in Patients with Gastric Cancer.
Background: Disease-related malnutrition, as a major cause of morbidity and mortality in cancer patients, is very common in patients with gastric cancer (GC). Malnutrition in cancer patients was reported to have important adverse effects, including a decreased response and tolerance to treatment, a decrease of performance, shorter survival, and lower quality of life. The treatment approaches involving chemotherapy is known to develop various acute and chronic symptoms that restrict eating and, thereby, exert a profound impact on nutritional status.Method: In this study, 82 patients with GC with an average age of 48.33 ± 10.74 were enrolled. Patients were followed up for 6 months without any nutritional intervention and/or education. A 168 item semi-quantities food frequency questioner was completed by a trained nutritionist at the beginning of the study and six months after the start of chemotherapy.Results: Intake of vitamin A (T0:585.52 ± 203.34 vs. T6:529.48 ± 138.91, t = 2.96), Thiamin (T0:2.09 ± 0.76 vs. T6:1.80 ± 0.72, t = 2.81), vitamin B6 (T0:2.03 ± 0.53 vs. T6:2.29 ± 0.73, t = 2.56), and vitamin B12 (T0:5.79 ± 3.96 vs. T6:4.48 ± 2.20, t = 2.43) significantly decreased after 6 months of receiving chemotherapy. On the other intake of beef (T0:17.79 ± 25.48 vs. T6:12.58 ± 16.66, t = 2.06), low-fat milk (T0:52.57 ± 69.80 vs. T6:29.18 ± 45.89, t = 2.95), cream (T0:2.42 ± 4.16 vs. T6:1.06 ± 1.68, t = 2.88), and raw vegetable (T0:6.54 ± 9.55 vs. T6:3.85 ± 5.23, t = 2.54) significantly decreased.Conclusion: Nutritional deterioration is an important part of the pathogenesis of cancer and its treatment that can occur at any point in the timeline of cancer diagnosis, treatment or support. Therefore nutritional counseling and supportive services are needed for cancer patients, especially when their disease is diagnosed.


Deep sequencing-based transcriptome profiling reveals comprehensive insights into the responses of Nicotiana benthamiana to beet necrotic yellow vein virus infections containing or lacking RNA4.
Beet necrotic yellow vein virus (BNYVV), encodes either four or five plus-sense single stranded RNAs and is the causal agent of sugar beet rhizomania disease, which is widely distributed in most regions of the world. BNYVV can also infect Nicotiana benthamiana systemically, and causes severe curling and stunting symptoms in the presence of RNA4 or mild symptoms in the absence of RNA4. Confocal laser scanning microscopy (CLSM) analyses showed that the RNA4-encoded p31 protein fused to the red fluorescent protein (RFP) accumulated mainly in the nuclei of N. benthamiana epidermal cells. This suggested that severe RNA4-induced symptoms might result from p31-dependent modifications of the transcriptome. Therefore, we used next-generation sequencing technologies to analyze the transcriptome profile of N. benthamiana in response to infection with different isolates of BNYVV. Comparisons of the transcriptomes of mock, BN3 (RNAs 1+2+3), and BN34 (RNAs 1+2+3+4) infected plants identified 3,016 differentially expressed transcripts, which provided a list of candidate genes that potentially are elicited in response to virus infection. Our data indicate that modifications in the expression of genes involved in RNA silencing, ubiquitin-proteasome pathway, cellulose synthesis, and metabolism of the plant hormone gibberellin may contribute to the severe symptoms induced by RNA4 from BNYVV. These results expand our understanding of the genetic architecture of N. benthamiana as well as provide valuable clues to identify genes potentially involved in resistance to BNYVV infection. Our global survey of gene expression changes in infected plants reveals new insights into the complicated molecular mechanisms underlying symptom development, and aids research into new strategies to protect crops against viruses.


Management of catheter-related upper extremity deep vein thrombosis in patients with cancer: A systematic review and meta-analysis.
Patients with cancer commonly require a central venous catheter, which is associated with an increased risk of venous thromboembolism (VTE). Despite the frequent occurrence, the optimal anticoagulation management and outcomes for patients with cancer and catheter-related upper extremity deep vein thrombosis (DVT) are unclear. We performed a systematic review and meta-analysis to evaluate the rates of recurrent VTE and bleeding in patients with cancer and catheter-related upper extremity DVT. We searched MEDLINE, Embase, Scopus, and CENTRAL from inception to June 2, 2023. The primary efficacy outcome was recurrent VTE, and the primary safety outcome was major bleeding. The incidence rates (with 95% confidence interval [CI]) of outcomes were pooled using random effects model. We included 29 studies (N=2,836), among which 5 were prospective. The duration of follow-up and anticoagulation varied considerably. The main long-term anticoagulant used was low-molecular-weight heparin, followed by direct oral anticoagulants. The pooled 3-month recurrent VTE rate from 14 studies (N=1128) was 0.56% (95% CI 0.10-3.01%, I2 = 0%). The pooled 3-month major bleeding rate from 10 studies (N=834) was 2.34% (95% CI 1.14-4.76%, I2 = 0%). We were unable to pool event rates beyond 3 months given high heterogeneity. All studies had serious risk of bias. Our study demonstrated a relatively low rate of recurrent VTE and moderate rate of major bleeding events within the first 3 months in patients with cancer and catheter-related upper extremity DVT. However, there was significant heterogeneity in the management and reporting after 3 months.


Possible Association of Polymorphisms in Ubiquitin Specific Peptidase 46 Gene With Post-traumatic Stress Disorder.
Introduction: Dynamic proteolysis, through the ubiquitin-proteasome system, has an important role in DNA transcription and cell cycle, and is considered to modulate cell stress response and synaptic plasticity. We investigated whether genetic variants in the ubiquitin carboxyl-terminal hydrolase 46 (USP46) would be associated with post-traumatic stress disorder (PTSD) in people with exposure to combat trauma using a case-control candidate gene association design. Methods: Korean male veterans exposed to the Vietnam War were grouped into those with (n = 128) and without (n = 128) PTSD. Seven tagging SNPs of USP46 were selected, and single-marker and haplotype-based association analyses were performed. All analyses were adjusted for sociodemographic factors and levels of combat exposure severity and alcohol problem. Results: One single-marker (rs2244291) showed nominal evidence of association with PTSD status and with the "re-experiencing" cluster, although the association was not significant after Bonferroni correction. No significant association with the other SNPs or the haplotypes was detected. Conclusion: The present finding suggests preliminarily that genetic vulnerability regarding the ubiquitin-proteasome system may be related to fear memory processes and the development of PTSD symptoms after trauma exposure. Further studies with a larger sample size will be needed to examine the role of the ubiquitin-proteasome system including USP46 in PTSD.


Cardiomyogenic differentiation of human bone marrow-derived mesenchymal stem cell spheroids within electrospun collagen nanofiber mats.
Collagen is the major structural protein in myocardium and contributes to tissue strength and integrity, cellular orientation, and cell-cell and cell-matrix interactions. Significant post-myocardial infarction related loss of cardiomyocytes and cardiac tissue, and their subsequent replacement with fibrous scar tissue, negatively impacts endogenous tissue repair and regeneration capabilities. To overcome such limitations, tissue engineers are working toward developing a 3D cardiac patch which not only mimics the structural, functional, and biological hierarchy of the native cardiac tissue, but also could deliver autologous stem cells and encourage their homing and differentiation. In this study, we examined the utility of electrospun, randomly-oriented, type-I collagen nanofiber (dia = 789 ± 162 nm) mats on the cardiomyogenic differentiation of human bone marrow-derived mesenchymal stem cells (BM-MSC) spheroids, in the presence or absence of 10 μM 5-azacytidine (aza). Results showed that these scaffolds are biocompatible and enable time-dependent evolution of early (GATA binding protein 4: GATA4), late (cardiac troponin I: cTnI), and mature (myosin heavy chain: MHC) cardiomyogenic markers, with a simultaneous reduction in CD90 (stemness) expression, independent of aza-treatment. Aza-exposure improved connexin-4 expression and sustained sarcomeric α-actin expression, but provided only transient improvement in cardiac troponin T (cTnT) expression. Cell orientation and alignment significantly improved in these nanofiber scaffolds over time and with aza-exposure. Although further quantitative in vitro and in vivo studies are needed to establish the clinical applicability of such stem-cell laden collagen nanofiber mats as cardiac patches for cardiac tissue regeneration, our results underscore the benefits of 3D milieu provided by electrospun collagen nanofiber mats, aza, and spheroids on the survival, cardiac differentiation and maturation of human BM-MSCs. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 106A: 3303-3312, 2018.


Risk of Hospital-Acquired Acute Kidney Injury among Adult Opioid Analgesic Users: A Multicenter Real-World Data Analysis.
Comprehensive data on the risk of hospital-acquired (HA) acute kidney injury (AKI) among adult users of opioid analgesics are lacking. This study aimed to systematically compare the risk of HA-AKI among the users of various opioid analgesics. This multicenter, retrospective real-world study analyzed 255,265 adult hospitalized patients who received at least one prescription of opioid analgesic during the first 30 days of hospitalization. The primary outcome was the time from the first opioid analgesic prescription to HA-AKI occurrence. 12 subtypes of opioid analgesics were analyzed, including 9 for treating moderate-to-severe pain and 3 for mild-to-moderate pain. We examined the association between the exposure to each subtype of opioid analgesic and the risk of HA-AKI using Cox proportional hazards models, using the most commonly used opioid analgesic as the reference group. As compared to dezocine, the most commonly used opioid analgesic for treating moderate-to-severe pain, exposure to morphine, but not the other 7 types of opioid analgesics, was associated with a significantly increased risk of HA-AKI (adjusted hazard ratio: 1.56, 95% confidence interval: 1.40-1.78). The association was consistent in stratified analyses and in a propensity-matched cohort. There were no significant differences in the risk of HA-AKI among the opioid analgesic users with mild-to-moderate pain after adjusting for confounders. The use of morphine was associated with an increased risk of HA-AKI in adult patients with moderate-to-severe pain. Opioid analgesics other than morphine should be chosen preferentially in adult patients with high risk of HA-AKI when treating moderate-to-severe pain.


Phosphatidylinositol 3-kinase contributes to cell volume regulation through effects on ATP release.
Regulated changes in cell volume represent a signal that modulates a broad range of cell and organ functions. In HTC hepatoma cells, increases in volume are coupled to membrane ion permeability through a pathway involving (i) ATP efflux, (ii) autocrine stimulation of P2 receptors, and (iii) increases in anion permeability and Cl- efflux, contributing to recovery of volume toward basal values. Based on recent evidence that cell volume increases also stimulate phosphoinositide kinases, the purpose of these studies was to determine if phosphatidylinositol 3-kinase (PI 3-kinase) modulates these pathways. Exposure of cells to hypotonic buffer (20 or 40% less NaCl) caused an initial increase in cell volume and stimulated a rapid increase in ATP release. Subsequent opening of Cl- channels was followed by recovery of cell volume toward basal values, despite the continuous presence of hypotonic buffer. Inhibition of PI 3-kinase with wortmannin (Ki = 3 nM) significantly inhibited both the rate of volume recovery and activation of Cl- currents; similar results were obtained with LY294002 (10 microM). Additionally, current activation was inhibited by intracellular dialysis with antibodies specific for the 110-kDa catalytic subunit of PI 3-kinase. Since release of ATP is a critical element in the volume-regulatory pathway, the role of PI 3-kinase on volume-stimulated ATP release was assessed. Both wortmannin and LY294002 decreased basal and volume-stimulated ATP permeability but had no effect on the current response to exogenous ATP (10 microM). These findings indicate that PI 3-kinase plays a significant role in regulation of cell volume and suggest that the effects are mediated in part through modulation of cellular ATP release.


Sex differences in fatigability and recovery relative to the intensity-duration relationship.
Females demonstrate greater fatigue resistance than males during contractions at intensities relative to maximum force. However, previous studies have not accounted for the influence of metabolic thresholds on fatigability. This study is the first to test whether sex differences in fatigability exist when exercise intensity is normalised relative to a metabolic threshold: the critical intensity derived from assessment of the intensity-duration relationship during intermittent, isometric knee extensor contractions. We show that critical intensity in females occurred at a higher percentage of maximum force compared to males. Furthermore, females demonstrated greater fatigue resistance at exercise intensities above and below this metabolic threshold. Our data suggest that the sex difference was mediated by lesser deoxygenation of the knee extensors during exercise. These data highlight the importance of accounting for metabolic thresholds when comparing fatigability between sexes, whilst emphasising the notion that male data are not generalisable to female populations. Females are less fatigable than males during isometric exercise at intensities relative to maximal voluntary contraction (MVC); however, whether a sex difference in fatigability exists when exercise is prescribed relative to a critical intensity is unknown. This study established the intensity-duration relationship, and compared fatigability and recovery between sexes following intermittent isometric contractions normalised to critical intensity. Twenty participants (10 females) completed four intermittent isometric knee extension trials to task failure to determine critical intensity and the curvature constant (W'), followed by fatiguing tasks at +10% and -10% relative to critical intensity. Neuromuscular assessments were completed at baseline and for 45 min post-exercise. Non-invasive neurostimulation, near-infrared spectroscopy, and non-invasive haemodynamic monitoring were used to elucidate the physiological mechanisms responsible for sex differences. Females demonstrated a greater critical intensity relative to MVC than males (25 ± 3 vs. 21 ± 2% MVC, P = 0.003), with no sex difference for W' (18,206 ± 6331 vs. 18,756 ± 5762 N s, P = 0.850). Time to task failure was greater for females (62.37 ± 17.25 vs. 30.43 ± 12.75 min, P < 0.001) during the +10% trial, and contractile function recovered faster post-exercise (P = 0.034). During the -10% trial females experienced less contractile dysfunction (P = 0.011). Throughout the +10% trial, females demonstrated lesser decreases in deoxyhaemoglobin (P = 0.007) and an attenuated exercise pressor reflex. These data show that a sex difference in fatigability exists even when exercise is matched for critical intensity. We propose that greater oxygen availability during exercise permits females to sustain a higher relative intensity than males, and is an explanatory factor for the sex difference in fatigability during intermittent, isometric contractions.


Carboplatin, doxorubicin, and cyclophosphamide versus cisplatin, doxorubicin, and cyclophosphamide: a randomized trial in stage III-IV epithelial ovarian carcinoma.
One hundred sixty-four patients with stage III-IV epithelial ovarian carcinoma were randomized to receive cisplatin (CDDP) 50 mg/mq, doxorubicin 45 mg/mq, and cyclophosphamide 600 mg/mq (PAC) or carboplatin 200 mg/mq, doxorubicin 45 mg/m2, and cyclophosphamide 600 mg/mq (CAC). To administer equitoxic doses at each cycle, the drug dosages were adjusted according to the hematologic toxicities experienced after the previous course; 44.7% of CAC and 21.1% of PAC patients required a dosage reduction at the second course (P = .002). Neither CAC nor PAC caused any clinically relevant neuro-nephrotoxicity; however, CDDP was administered with hydration and forced diuresis, while carboplatin was administered by rapid intravenous (IV) infusion. After six cycles, response rates were superimposable: 62.5% and 66.6% for CAC and PAC, respectively; pathologic complete responses (pCRs) were 16.7% for CAC and 23.2% for PAC; among patients with more than 2 cm residual disease, PAC induced more pCRs than CAC (eight of 52 or 15.4% v one of 42 or 2.4%, P = .07). Median survivals and progression-free survivals (PFSs) were 22.6 and 13.2 months for PAC, and 23.1 and 15.5 months for CAC, respectively; these differences are not significant. In conclusion, this trial demonstrates that equitoxic doses of PAC or CAC result in a similar response rate, PFS, and survival.


A hospital-based strategy for setting priorities for antiviral prophylaxis during an influenza pandemic.
An influenza pandemic would place an unprecedented strain on the nation's healthcare system-a compelling reason to carefully plan how priorities would be set for distributing antiviral medications. While antiviral medications have been added to the Strategic National Stockpile (SNS), these supplies are not designated as frontline resources and remain far from sufficient to provide mass prophylaxis for the entire population of the country. In the healthcare setting, providing general chemoprophylaxis may not be feasible because of high costs or inadequate supply. We propose a hospital-based strategy for setting priorities for antiviral prophylaxis that may offer a rational starting point for discussion and guide allocation decisions in the event of a shortage during a pandemic influenza outbreak.


Successful management of postinfarction ventricular septal rupture.
Ventricular septal rupture is a rare but devastating complication of acute myocardial infarction. Especially in patients with cardiogenic shock, right ventricular dysfunction or an inferior infarct mortality is very high. We present a case in which an 83-year-old patient survived rupture of the ventricular septum complicating an inferior myocardial infarction. Unlike most patients his haemodynamic status did not deteriorate and delayed elective surgical repair was carried out successfully.


In vitro evaluation of a compliant inflow cannula reservoir to reduce suction events with extracorporeal rotary ventricular assist device support.
Limited preload sensitivity of rotary left ventricular assist devices (LVADs) renders patients susceptible to harmful atrial or ventricular suction events. Active control systems may be used to rectify this problem; however, they usually depend on unreliable sensors or potentially inaccurate inferred data from, for example, motor current. This study aimed to characterize the performance of a collapsible inflow cannula reservoir as a passive control system to eliminate suction events in extracorporeal, rotary LVAD support. The reservoir was evaluated in a mock circulation loop against a rigid cannula under conditions of reduced preload and increased LVAD speed in both atrial and ventricular cannulation scenarios. Both cases demonstrated the ease with which chamber suction events can occur with a rigid cannula and confirm that the addition of the reservoir maintained positive chamber volumes with reduced preload and high LVAD speeds. Reservoir performance was dependent on height with respect to the cannulated chamber, with lower placement required in atrial cannulation due to reduced filling pressures. This study concluded that a collapsible inflow cannula is capable of minimizing suction events in extracorporeal, rotary LVAD support.


[Series: Communication in the dental practice. Building a good dentist-patient relationship with communication].
A good dentist-patient relationship promotes better oral health of the patient. In order to build and maintain such a relationship a dentist should possess good communication skills. First of all, an open, empathic attitude is important, in which the dentist is aware that he can make mistakes interpreting patient behaviour. Good observational skills are necessary to detect (non-)verbal signals indicating how to interpret the patient's story. By demonstrating non-verbal, paralingual and verbal listening behaviour,he can show patients that he is paying attention to them. When discussing findings, it is important for patients to receive a clear explanation and be given the opportunity to ask questions. It is also wise to pay attention to the patient's expectations of the treatment outcome, elaborate on the advantages and disadvantages of the treatment alternatives and to be transparent in case of complications.


The novel CDK9 inhibitor, XPW1, alone and in combination with BRD4 inhibitor JQ1, for the treatment of clear cell renal cell carcinoma.
Clear cell renal cell carcinoma (ccRCC) is a highly lethal malignancy with few therapeutic options. Cyclin‑dependent kinase 9 (CDK9), a potential therapeutic target of many cancers, has been recently observed to be upregulated in ccRCC patients. Therefore, we aimed to investigate the therapeutic potential of CDK9 in ccRCC and develop a novel CDK9 inhibitor with low toxicity for ccRCC treatment. The expression of CDK9 in ccRCC was checked using the online database and tissue microarray analysis. shRNA-mediated CDK9 knockdown and CDK inhibitor were applied to evaluate the effect of CDK9 on ccRCC. Medicinal chemistry methods were used to develop a new CDK9 inhibitor with drugability. RNA-seq and ChIP-seq experiments were conducted to explore the mechanism of action. MTS, western blotting, and colony formation assays were performed to evaluate the anti-ccRCC effects of CDK9 knockdown and inhibition in vitro. The in vivo anti-tumour efficacy was evaluated in a xenograft model. CDK9 is overexpressed and associated with poor survival in ccRCC. Knockdown or inhibition of CDK9 significantly suppressed ccRCC cells. XPW1 was identified as a new potent and selective CDK9 inhibitor with excellent anti-ccRCC activity and low toxicity. In mechanism, XPW1 transcriptionally inhibited DNA repair programmes in ccRCC cells, resulting in an excellent anti-tumour effect. CDK9 and BRD4 were two highly correlated transcriptional regulators in ccRCC patients, and the BRD4 inhibitor JQ1 enhanced XPW1's anti-ccRCC effects in vitro and in vivo. This work provides valuable insights into the therapeutic potential of CDK9 in ccRCC. The CDK9 inhibitor XPW1 would be a novel therapeutic agent for targeting ccRCC, alone or in rational combinations.


Patient and practice perspectives on strategies for controlling blood pressure, North Carolina, 2010-2012.
Patient and practice perspectives can inform development of team-based approaches to improving blood pressure control in primary care. We used a community-based participatory research approach to assess patient and practice perceptions regarding the value of team-based strategies for controlling blood pressure in a rural North Carolina population from 2010 through 2012. In-depth interviews were conducted with 41 adults with hypertension, purposely sampled to include diversity of sex, race, literacy, and blood pressure control, and with key office staff at 5 rural primary care practices in the southeastern US "stroke belt." Interviews explored barriers to controlling blood pressure, the practice's role in controlling blood pressure, and opinions on the use of team care delivery. Patients reported that provider strategies to optimize blood pressure control should include regular visits, medication adjustment, side-effect discussion, and behavioral counseling. When discussing team-based approaches to hypertension care, patients valued verbal encouragement, calls from the doctor's office, and the opportunity to ask questions. However, they voiced concerns about the effect of having too many people involved in their care. Practice staff focused on multiple, broad methods to control blood pressure including counseling, regular office visits, media to improve awareness, and support groups. An explicit focus of delivering care as teams was a newer concept. When developing a team approach to hypertension treatment, patients value high-quality communication and not losing their primary relationship with their provider. Practice staff members were open to a team-based approach but had limited knowledge of what such an approach would entail.


[Study of the conformational situation in an aqueous solution of dinucleoside phosphates using proton spin lattice relaxation].
With the use of experimentally measured spin-lattice relaxation rates of H(5), H(6), H(2), H(8) and H(1') the analysis of the conformational situation in aqueous solution of CpC, CpA, ApC and ApA has been carried out. In all cases, the close state is shown to be described by the equilibrium of right- and left-handed forms. The right-handed forms are favourable for all DNP studied and are related to the "canonical" Pba type. On the contrary, the possibility of realization of one or the other noncanonical forms (these are mainly left-handed conformers) is determined strictly by nucleotide sequences. The noncanonical conformers for CpC and CpA are Mbb forms, in which both monomeric units are characterized by anti-conformation, and the base of the 3'-end is turned 180 degrees around the glycosidic bond as compared to the canonical form. The forms of Mab type are possible for ApC. In this case, the purine monomer exists in syn-, but the pyrimidine monomer--in anti-conformation. Both bases are turned to 180 degrees. Finally, in the case of ApA, the forms of Mba type with high-anti-conformation of both monomers are realized. The conformational behaviour of oligonucleotides and the possible biological role of noncanonical conformations are discussed taking into consideration the results obtained.


Acute Effects of Elastic Bands on Kinetic Characteristics During the Deadlift at Moderate and Heavy Loads.
Loading a barbell with variable resistance positively alters kinetic characteristics during the back squat and bench press but has never been studied during the deadlift. The purpose of this project was to examine the acute effects of combining elastic bands and free weights during the deadlift at moderate and heavy loads. Twelve trained men (age: 24.08 ± 2.35 years, height: 175.94 ± 5.38 cm, mass: 85.58 ± 12.49 kg, deadlift 1 repetition maximum (RM): 188.64 ± 16.13 kg) completed 2 variable resistance (B1 and B2) and 1 traditional free-weight (NB) condition at both 60 and 85% 1RM on a force plate. B1 had 15% resistance from bands, with the remaining 85% from free weights. B2 had 35% bands and 65% free weights. NB used free weights only. Average resistance was equated for all conditions. Power and velocity generally increased, whereas force decreased with the addition of bands. The amount of band tension (B1 or B2) had little impact on power when lifting at 60% 1RM. However, greater resistance from bands resulted in greater peak and relative power when lifting at 85% 1RM. Adding elastic bands decreased time to peak force (PF), time between PF and peak power (PP), and time between PF and peak velocity (PV) when compared with NB at 60% 1RM (NB > B1 > B2). These differences only reached significance for NB > B2 when lifting at 85% 1RM. These same differences existed for time between PP and PV. Thus, the amount of tension from bands has less impact on interpeak variables at heavier absolute loads. Practitioners should consider using heavy bands when prescribing the deadlift for speed or power, but not maximal force.


Compliance with surgical smoke evacuation guidelines: implications for practice.
Surgical smoke presents a serious health hazard, but perioperative nurses' compliance with smoke evacuation recommendations is not consistent. I investigated key indicators for compliance with electrosurgical smoke evacuation recommendations based on nurses' individual innovativeness characteristics, perceptions of the attributes of smoke evacuation recommendations, and organizational innovativeness characteristics. The study findings provide implications for improving nurses' compliance with smoke evacuation recommendations. Individual innovativeness characteristics, including nurses' knowledge and training, were most strongly linked to smoke evacuation compliance. The key indicators that promote surgical smoke evacuation can provide direction to guide the content of education programs and help identify the personnel and settings that are most in need of this information. Barriers to compliance included lack of equipment, physician resistance, noise, and staff member complacency. Vendor demonstrations on the ease of smoke evacuation device use can show nurses that smoke evacuation is compatible with nursing practice. Facility leaders should provide smoke evacuation policies that are easy to understand and should enforce these policies.


The reduction potential of the beta-carotene.+ /beta-carotene couple in an aqueous micro-heterogeneous environment.
There is a resurgence of interest in the role of electron transfer reactions involving beta-carotene in photosynthesis. There is also current debate on the health benefits of dietary carotenoids and the possible deleterious effects on certain sub-populations such as smokers. The impact of dietary carotenoids on health may well be also related to radical reactions. A key parameter in biological systems is therefore the one-electron reduction potential of the carotenoid radical cation, now reported for the first time in a model biological aqueous environment. The value obtained is 1.06+/-0. 01 V and is sufficiently high to oxidise cell membrane proteins, but is low enough to repair P(680).+ in the photosynthetic reaction centre.


Three-Dimensional Eyeball and Orbit Volume Modification After LeFort III Midface Distraction.
The aim of our study was to evaluate orbital volume modification with LeFort III midface distraction in patients with craniosynostosis and its influence on eyeball volume and axial diameter modification. Orbital volume was assessed by the semiautomatic segmentation method based on deformable surface models and on 3-dimensional (3D) interaction with haptics. The eyeball volumes and diameters were automatically calculated after manual segmentation of computed tomographic scans with 3D slicer software. The mean, minimal, and maximal differences as well as the standard deviation and intraclass correlation coefficient (ICC) for intraobserver and interobserver measurements reliability were calculated. The Wilcoxon signed rank test was used to compare measured values before and after surgery. P < 0.05 was considered statistically significant. Intraobserver and interobserver ICC for haptic-aided semiautomatic orbital volume measurements were 0.98 and 0.99, respectively. The intraobserver and interobserver ICC values for manual segmentation of the eyeball volume were 0.87 and 0.86, respectively. The orbital volume increased significantly after surgery: 30.32% (mean, 5.96 mL) for the left orbit and 31.04% (mean, 6.31 mL) for the right orbit. The mean increase in eyeball volume was 12.3%. The mean increases in the eyeball axial dimensions were 7.3%, 9.3%, and 4.4% for the X-, Y-, and Z-axes, respectively. The Wilcoxon signed rank test showed that preoperative and postoperative eyeball volumes, as well as the diameters along the X- and Y-axes, were statistically significant. Midface distraction in patients with syndromic craniostenosis results in a significant increase (P < 0.05) in the orbit and eyeball volumes. The 2 methods (haptic-aided semiautomatic segmentation and manual 3D slicer segmentation) are reproducible techniques for orbit and eyeball volume measurements.


Incidence of bleeding after 15,181 percutaneous biopsies and the role of aspirin.
The objective of our study was to report the incidence of bleeding after imaging-guided percutaneous core biopsy at a single center using a standardized technique. We performed a retrospective review of percutaneous core biopsies performed at our institution from January 2002 through February 2008. Data were collected at the time of biopsy, and clinical information was obtained 24 hours and 3 months after the biopsy. The specific information that was collected included the results of coagulation studies, aspirin use, the organ biopsied, the size of the biopsy needle, and the number of needle passes. Bleeding complications were defined using the Common Terminology Criteria for Adverse Events (CTCAE, version 3.0) established by the National Cancer Institute. Among the 15,181 percutaneous core biopsies performed during the study period, 70 hemorrhages (0.5%) that were CTCAE grade 3 or greater were identified within 3 months of biopsy. The incidence of bleeding in patients taking aspirin within 10 days before biopsy was 0.6% (18/3,195), which was not statistically different compared with the incidence of bleeding in those not taking aspirin (52/11,986, 0.4%; p = 0.34). The incidence of bleeding after liver biopsy was 0.5%; kidney biopsy, 0.7%; lung biopsy, 0.2%; pancreas biopsy, 1.0%; and other biopsy, 0.2%. There were significant associations between major bleeding and serum platelet count and international normalized ratio (p < 0.001), although the association between major bleeding and the size of the biopsy needle was not significant (p = 0.97). The overall incidence of major bleeding after imaging-guided percutaneous core needle biopsy is low. Recent aspirin therapy does not appear to significantly increase the risk of such bleeding complications.


Management of sinonasal inverted papillomas and comparison of classification staging systems.
The aim of this study was to describe treatment results in patients with sinonasal inverted papilloma and to compare recent classification staging systems. We performed a retrospective study of 79 patients with primary paranasal sinus inverted papilloma from 1978 to 2008. The median age at diagnosis was 59 years. There were 68 men (86%) and 11 women (14%). Sixty inverted papilloma (76%) were located in the ethmoidal sinus complex, 16 (20%) were in the maxillary sinus, 2 were in the sphenoid sinus (3%), and 1 was in the septum (1%). Malignancy was simultaneously associated in four cases (5%). Intracranial extension was found in five patients (6%) and we did not find orbital content involvement. The external approach was used in 22 cases (28%) and 57 patients were treated with endoscopic nasal resection (72%). The overall recurrence rate in the total population was 21%. Recurrences were observed in 7 cases (32%) in the group of patients who received external approach and in 10 (17%) patients in the endoscopic group. Recurrences according to the Krouse system were 0% in T1 stage, 16% in T2 stage, 25% in T3 stage, and 60% in T4 stage (p = 0.05). Recurrences for groups A, B, and C stages using the Cannady staging system were 12, 26, and 60%, respectively (p = 0.039). Recurrences according to Han's system were 19% in both T1 and T2, 20% in T3, and 60% in T4 (p > 0.05). Our results support the endoscopic approach as the treatment of choice when feasible in patients with inverted papilloma, combined in selected cases with external approaches. The Krouse and Cannady systems provided a good distribution of patients according to local control.


Distributed Egocentric Betweenness Measure as a Vehicle Selection Mechanism in VANETs: A Performance Evaluation Study.
In the traditional approach for centrality measures, also known as sociocentric, a network node usually requires global knowledge of the network topology in order to evaluate its importance. Therefore, it becomes difficult to deploy such an approach in large-scale or highly dynamic networks. For this reason, another concept known as egocentric has been introduced, which analyses the social environment surrounding individuals (through the ego-network). In other words, this type of network has the benefit of using only locally available knowledge of the topology to evaluate the importance of a node. It is worth emphasizing that in this approach, each network node will have a sub-optimal accuracy. However, such accuracy may be enough for a given purpose, for instance, the vehicle selection mechanism (VSM) that is applied to find, in a distributed fashion, the best-ranked vehicles in the network after each topology change. In order to confirm that egocentric measures can be a viable alternative for implementing a VSM, in particular, a case study was carried out to validate the effectiveness and viability of that mechanism for a distributed information management system. To this end, we used the egocentric betweenness measure as a selection mechanism of the most appropriate vehicle to carry out the tasks of information aggregation and knowledge generation. Based on the analysis of the performance results, it was confirmed that a VSM is extremely useful for VANET applications, and two major contributions of this mechanism can be highlighted: (i) reduction of bandwidth consumption; and (ii) overcoming the issue of highly dynamic topologies. Another contribution of this work is a thorough study by implementing and evaluating how well egocentric betweenness performs in comparison to the sociocentric measure in VANETs. Evaluation results show that the use of the egocentric betweenness measure in highly dynamic topologies has demonstrated a high degree of similarity compared to the sociocentric approach.


Don't ask me where I'm from: thoughts of immigrants to Catalonia on social integration and cultural capital.
Once you get here, you realize that thinking Foucault was writing for you was terribly naïve, since in reality I did not exist as a subject for anyone like Foucault, or if I did it was only as an object of study', recalls one of the protagonists in this essay, a collage of fragments of interviews with foreign immigrants from impoverished countries who have settled in Barcelona and other Catalan towns in recent years. Widespread prejudice in the host society dictates that these people are generalized as being on a lower cultural level, anonymous members of the growing mass of immigrants prepared to work at any price. The prejudice seems to be confirmed by the fact that the great majority of them do low-skilled or unskilled work in sectors such as the building trade, hotels and restaurants and domestic service. The reality, however, is very different. The average level of formal education of these immigrants is similar to that of the host population. It is the precariousness of their legal status or the often insurmountable barriers preventing recognition of their academic and/or professional qualifications, or simply cultural prejudice, that condemn them to accept jobs well below their personal potential. Thus, the host society wastes social and cultural capital of the first order, and lays foundations for a permanent division between 'us' and 'them'. This essay offers a modest but revealing sample of the quality and diversity of the ideas and viewpoints of the immigrants themselves, an asset we continue to at best underestimate or more often ignore altogether.


Determining factors in evidence-based clinical practice among hospital and primary care nursing staff.
The general aim of this study is to identify key factors perceived by nurses to influence evidence-based clinical practice at different centres. During the last decade, there has been an increased interest in the identification of factors that facilitate the transfer of knowledge into clinical practice, among health care professionals. Previous research states that a suitable organisational framework and practice environment seems to have influence on a greater use of scientific evidence by nurses, which can be directly observed in patient outcomes. In consequence, several authors suggest that strategies should be encouraged from managers and nurse executives to guarantee the existence of environments that avoid emotional exhaustion and improve satisfaction of nurses with their work, and at the same time, ensure the use of research-guided nursing decisions. Following the Spanish validation of the Practice Environment Scale-Nursing Work Index and Evidence Based Practice Questionnaire, a descriptive observational cross-sectional study has been conceived, from 2010 to 2011, in order to identify determining factors in evidence-based clinical practice at different centres. In a second phase, a qualitative study has been designed, using focus groups, to identify practice factors that can lead to a successful implementation of evidence-based clinical practice. Organisational and attitudinal interventions are needed in order to implement evidence-based clinical practice that improves the quality of patient care.


Structures of the compact helical core domains of feline calicivirus and murine norovirus VPg proteins.
We report the solution structures of the VPg proteins from feline calicivirus (FCV) and murine norovirus (MNV), which have been determined by nuclear magnetic resonance spectroscopy. In both cases, the core of the protein adopts a compact helical structure flanked by flexible N and C termini. Remarkably, while the core of FCV VPg contains a well-defined three-helix bundle, the MNV VPg core has just the first two of these secondary structure elements. In both cases, the VPg cores are stabilized by networks of hydrophobic and salt bridge interactions. The Tyr residue in VPg that is nucleotidylated by the viral NS7 polymerase (Y24 in FCV, Y26 in MNV) occurs in a conserved position within the first helix of the core. Intriguingly, given its structure, VPg would appear to be unable to bind to the viral polymerase so as to place this Tyr in the active site without a major conformation change to VPg or the polymerase. However, mutations that destabilized the VPg core either had no effect on or reduced both the ability of the protein to be nucleotidylated and virus infectivity and did not reveal a clear structure-activity relationship. The precise role of the calicivirus VPg core in virus replication remains to be determined, but knowledge of its structure will facilitate future investigations.


Utility of Intraprocedural Contrast-Enhanced CT in Ablation of Renal Masses.
OBJECTIVE. The purpose of this study was to evaluate the efficacy of radiofrequency ablation (RFA) of renal masses comparing a group who did not undergo intraprocedural CT and a group who did. MATERIALS AND METHODS. A retrospective review included 45 consecutively registered patients who underwent RFA of renal masses. If an adequate biopsy specimen was not obtained or follow-up was inadequate, the patient was eliminated from review from calculation of primary technical efficacy. The inclusion criterion was having undergone RFA with two cooled-tip electrodes. Baseline demographics (age, body mass index, and sex), renal mass characteristics (diameter, side, location, position, morphologic features, type of mass, and grade), technical details (repositioning and hydrodissection), and complications were evaluated. Follow-up images were evaluated to determine the presence of recurrence at the ablation site in the two groups. RESULTS. Among the 45 patients who underwent RFA, 13 did not undergo intraprocedural CT and 32 intraprocedural did. Thirty-five patients met the criteria for follow-up and positive biopsy results. For calculation of recurrence, 10 patients were in the group who did not and 25 were in group who did undergo intraprocedural contrast-enhanced CT. No correlation was found between baseline demographics, renal mass characteristics, and technical results of the two groups. There was an 89% overall technical efficacy rate with a 96% primary technical efficacy rate in the group who underwent intraprocedural CT compared with a 70% rate in the group who did not undergo intraprocedural CT. Negative correlation was found between the groups with respect to technical efficacy rate at p < 0.05. CONCLUSION. Intraprocedural contrast-enhanced CT yields important information about completeness of ablation during the procedure, allowing probe repositioning and thus better therapeutic effect.


Memantine prevents the cognitive impairment induced by 3,4-methylenedioxymethamphetamine in rats.
Amphetamine abuse is an important risk factor for the development of cognitive impairment involving learning and memory. Since in previous studies we have demonstrated the effectiveness of alpha-7 nicotinic receptor antagonists in preventing the neurotoxicity induced by amphetamine derivatives, the present paper seeks to determine whether pre-treatment with memantine (MEM) (an antagonist of both nicotinic and NMDA receptors) counteracts the memory impairment induced by 3,4-methylenedioxymethamphetamine (MDMA or ecstasy) administration in male Long Evans rats. In mice, MDMA and MEM induced a locomotor stimulant response but with a different profile. Moreover, MEM inhibited the rearing and thygmotaxis behaviour induced by MDMA. Non-spatial memory was tested in the object recognition test and the spatial learning and memory was tested in the Morris water maze. In our experimental conditions, rats receiving MEM pre-treatment recovered the ability to discriminate between the familiar and the novel object that had been abolished by MDMA treatment. Animals treated with MDMA showed impaired learning in the Morris water maze. Results of the probe trial demonstrated that MDMA-treated rats did not remember the location of the platform, but this memory impairment was also prevented by the MEM pre-treatment. Moreover, MEM alone improved the learning task. No differences were observed between the different groups as regards swim speed. In conclusion, MEM significantly improved the learning and memory impairment induced by MDMA and constitutes the first approach to the treatment of the long-term cognitive deficits found in ecstasy users.


Decline in mortality, AIDS, and hospital admissions in perinatally HIV-1 infected children in the United Kingdom and Ireland.
To describe changes in demographic factors, disease progression, hospital admissions, and use of antiretroviral therapy in children with HIV. Active surveillance through the national study of HIV in pregnancy and childhood (NSHPC) and additional data from a subset of children in the collaborative HIV paediatric study (CHIPS). United Kingdom and Ireland. 944 children with perinatally acquired HIV-1 under clinical care. Changes over time in progression to AIDS and death, hospital admission rates, and use of antiretroviral therapy. 944 children with perinatally acquired HIV were reported in the United Kingdom and Ireland by October 2002; 628 (67%) were black African, 205 (22%) were aged > or = 10 years at last follow up, 193 (20%) are known to have died. The proportion of children presenting who were born abroad increased from 20% in 1994-5 to 60% during 2000-2. Mortality was stable before 1997 at 9.3 per 100 child years at risk but fell to 2.0 in 2001-2 (trend P < 0.001). Progression to AIDS also declined (P < 0.001). From 1997 onwards the proportion of children on three or four drug antiretroviral therapy increased. Hospital admission rates declined by 80%, but with more children in follow up the absolute number of admissions fell by only 26%. In children with HIV infection, mortality, AIDS, and hospital admission rates have declined substantially since the introduction of three or four drug antiretroviral therapy in 1997. As infected children in the United Kingdom and Ireland are living longer, there is an increasing need to address their medical, social, and psychological needs as they enter adolescence and adult life.


Electronic Health Record Recording of Patient Pain: Challenges and Discrepancies.
In the present review, various categories of pain, clinician-observed pain scales, and patient-reported pain scales are evaluated to better understand factors that impact patient pain perceptions. Additionally, the expansion of areas that require further research to determine the optimal way to evaluate pain scale data for treatment and management are discussed. Electronic health record (EHR) data provides a starting point for evaluating whether patient predictors influence postoperative pain. There are several ways to assess pain and choosing the most effective form of pain treatment. Identifying individuals at high risk for severe postoperative pain enables more effective pain treatment. However, there are discrepancies in patient pain reporting dependent on instruments used to measure pain and their storage in the EHR. Additionally, whether administered by a physician or another healthcare practitioner, differences in patient pain perception occur. While each scale has distinct advantages and limitations, pain scale data is a valuable therapeutic tool for assisting clinicians in providing patients with optimal pain control. Accurate assessment of patient pain perceptions by data extraction from electronic health records provides a potential for pain alleviation improvement. Predicting high-risk postoperative pain syndromes is a difficult clinical challenge. Numerous studies have been conducted on factors that impact pain prediction. Postoperative pain is significantly predicted by the kind of operation, the existence of prior discomfort, patient anxiety, and age.


Patient Preferences for Pharmacy Services: A Systematic Review of Studies Based on Discrete Choice Experiments.
In recent years, the mission of pharmacists has evolved and the model of the caregiver-patient relationship has been challenged by a new patient-centered approach. A challenge to providing personalized care is the assessment of patient preferences. We aimed to systematically identify published discrete choice experiments related to patient preferences for pharmacy services and to assess the quality of the selected articles. A systematic review of the literature was conducted in two databases (PubMed and Embase, until March 2023) according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) recommendations. The quality of the selected articles was assessed according to the International Society for Pharmacoeconomics and Outcomes Research conjoint analysis checklist. Among the 421 articles identified, 16 published studies were included and analyzed. They were mostly published in pharmaceutical (n = 6), economic (n = 4), and public health (n = 4) journals. Only two articles concerned the field of hospital pharmacy. Only five presented the specific pharmacy service studied: filling of prescriptions, management of symptoms, treatment delivery, and components of pharmacist counseling. Five articles focused on pharmacy services related to a specific disease. None fully fulfilled the International Society for Pharmacoeconomics and Outcomes Research checklist, only partially fulfilled. According to the identified studies, cost, time, logistics (organizational criteria), and pharmacists' courtesy and skills were consistently cited as factors influencing patient preferences for pharmacy services. The disclosure of patient preferences is a complex and under-researched topic, especially in the field of pharmacy, but interest is growing. As the mission of pharmacists evolves to bring them closer to patients, the better understanding of patient preferences in pharmacy services will allow for better targeting and better integration of patient profiles in patient management.


Fluorescence-guided surgery with indocyanine green to identify an idiopathic chyle leak-case report.
Chylothorax is the leakage of chyle into the pleural space and is associated with up to 50% morbidity. Although, the identification of traumatic chylothoraces is well described, non-traumatic chylothoraxes, mostly idiopathic, present therapeutic challenges as they are difficult to localize. We describe an attempt at localizing and treating an idiopathic chylothorax refractory to conservative and minimally invasive techniques. This was done using indocyanine green (ICG) and was a joint case between a thoracic surgeon and an interventional radiologist. A 50-year-old female with a recent history of coronavirus disease (COVID)-19 presented with shortness of breath. She was found to have a right pleural effusion and was admitted to the hospital, where a chest tube was inserted and pleural fluid analysis confirmed the diagnosis of a chylothorax. Conservative management was attempted but with little success. Initial magnetic resonance lymphangiogram (MRL) revealed abnormal enhancing lymphatic masses in the right paraspinal thoracic space as well as lympho-venous junction obstruction with large neck collaterals. She then underwent percutaneous lympho-venous junction angioplasty followed by multiple rounds of glue embolization without clinical improvement. The decision was then made to proceed with a thoracotomy, identification of the site of thoracic duct (TD) leakage, and a mechanical pleurodesis assisted by intraoperative imaging. Ten mg of ICG was injected into the inguinal lymph nodes. Using a camera capable of detection of near-infrared (NIR) light, we were able to visualize the site from which the ICG was extravasating in the chest. Glue was then injected in that area to further help in reducing the leak. After keeping her nil per os (NPO) and requiring one more ligation, a repeat MRL showed a markedly decreased leak into the right pleural space. Two weeks later, she was seen in clinic and reported significant improvement in her symptoms. This is the case of a 50-year-old female who was found to have a significant right chylothorax. She underwent conservative management, followed by tube thoracostomy, and TD ligation but was refractory to treatment. Fluorescence-guided surgery was pivotal to localize the leakage site and help seal it intraoperatively.


Alpha-Adrenergic Agonists Stimulate Fluid Secretion in Lacrimal Gland Ducts.
The role of adrenergic innervation in the regulation of lacrimal gland (LG) ductal fluid secretion is unknown. The Aim of the present study was to investigate the effect of adrenergic stimulation on fluid secretion in isolated LG duct segments and to study the underlying intracellular mechanisms. Fluid secretion of isolated mouse LG ducts was measured using video-microscopy. Effect of various adrenergic agonists (norepinephrine, phenylephrine, and isoproterenol) on fluid secretion as well as inhibitory effects of specific antagonists on adrenergic agonist-stimulated secretory response were analyzed. Changes in intracellular Ca2+ level [Ca2+i] were investigated with microfluorometry. Both norepinephrine and phenylephrine initiated a rapid and robust fluid secretory response, whereas isoproterenol did not cause any secretion. Phenylephrine-induced secretion was completely blocked by α1D-adrenergic receptor blocker BMY-7378. The endothelial nitric oxide synthase (eNOS) inhibitor L-NAME or guanylyl cyclase inhibitor ODQ reduced but not completely abolished the phenylephrine-induced fluid secretion, whereas co-administration of Ca2+-chelator BAPTA-AM resulted in a complete blockade. Phenylephrine stimulation induced a small, but statistically significant elevation in [\(Ca_i^{2 + }\)]. Our results prove the direct role of α1-adrenergic stimulation on LG ductal fluid secretion. Lack of isoproterenol-induced fluid secretory response suggests the absence of β-receptor mediated pathway in mouse LG ducts. Complete blockade of phenylephrine-induced fluid secretion by BMY-7378 and predominant inhibition of the secretory response either by L-NAME or ODQ suggest that α-adrenergic agonists use the NO/cGMP pathway through α1D receptor. Ca2+ signaling independent from NO/cGMP pathway may also play an at least partial role in α-adrenergic induced ductal fluid secretion.


Motivated shortcomings in explanation: the role of comparative self-evaluation and awareness of explanation recipient's knowledge.
Being aware of someone else's existing knowledge is a prerequisite to effectively adapting an explanation to that person's learning needs. However, such knowledge awareness introduces the potential for motivated self-evaluation based on relative knowledge, that is, for social comparison. Because favorable social comparisons are actively defended, we propose that knowledge awareness might undermine information sharing in explanation when social comparison motives are active. We tested this hypothesis in a series of experiments in which participants provided explanations to an ostensible learning partner with or without knowledge awareness. Both dispositionally and situationally motivated social comparison interacted with knowledge awareness to reduce information sharing in explanation. Intriguingly, knowledge awareness uniformly facilitated adaptation of the information that was shared to address partner knowledge deficit. These results illustrate a tension in the components of effective explanation. At the same time that knowledge awareness effectively coordinates explanation content, it can lead to knowledge hoarding by knowledgeable explainers who are motivated to rely on knowledge differences between the self and the explanation recipient for self-evaluation.


Outcomes and Correlates of Major Depression in 11 Disaster Studies Using Consistent Methods.
This study investigated psychosocial functioning and employment status in association with postdisaster major depression and its course in survivors of 11 different disasters in a sample of 808 directly-exposed survivors of 10 disasters and 373 survivors of the 11 September 2001 (9/11), terrorist attacks on New York City's World Trade Center (total n = 1181). Participants were assessed between 1987 and 2007 with structured diagnostic interviews in a prospective longitudinal design. Consistent research methods allowed merging of the disaster databases for analysis using multivariate modeling. Postdisaster major depression in the study cohort from the 9/11 disaster was more than twice as prevalent as in the other disasters, possibly reflecting the greater psychosocial/interpersonal loss and bereavement experienced by 9/11 disaster survivors. At follow up, employment was associated with remission of postdisaster major depression, non-development of PTSD, and coping via family or friends. Functioning problems were associated with disaster injuries, but not with persistent major depression. This study is unprecedented in its large sample of survivors across the full range of disaster typology studied using consistent methods and full structured interview diagnostic assessment. These findings may help guide future interventions to address postdisaster depression.


[Appropriateness of diagnostic tests in cardiovascular prevention: what can we skip?].
In recent years, a huge increase in the use of cardiac procedures, both invasive and non-invasive, was observed. Diagnostic tests, mainly non-invasive tests, are often prescribed inappropriately, in most cases replacing the clinical evaluation. The rate of inappropriate tests in cardiology is largely variable, depending on regional issues and different medical approach. When the test entails radiation exposure, the biological risk for both the patient and the environment must be taken into account. For this reason, the test that results in less biological risk should always be preferred as a first step.Moreover, it has not been clearly demonstrated that some diagnostic tests help to improve the outcome, that is to prevent cardiovascular events. As many as one sixth of the patients who undergo stress imaging are not taking proper medication, and very frequently no change in therapy is made after the test, regardless of the outcome. Since the appropriateness of diagnostic evaluation requests is mandatory, we focused on the diagnostic tests usually performed in primary and secondary prevention that carry no contribution to the clinical management of patients. This review addresses the need to optimize available resources, reduce costs and avoid unnecessary cardiovascular assessments, thereby enhancing the more efficient care delivery models.


Pre-operative clinical assessment for anaesthesia and the effect of HIV infection.
HIV infection is common in South Africa, often remaining clinically latent and liable to be missed during clinical pre-operative assessment, despite the patient having a severe degree of immune compromise. The primary objective was to determine the pre-operative physical status of patients presenting for anaesthesia, and to compare this with subsequent HIV tests and the CD4 counts of the HIV-positive patients. The secondary objective was to determine the prevalence of HIV infection in this group and in selected subgroups. A sample of 350 adult patients presenting for anaesthesia at Chris Hani Baragwanath Hospital were interviewed pre-operatively, examined, and their American Society of Anesthesiologists physical status grading determined. In those who were confirmed HIV positive by blood sample, a CD4 count was checked. Further data were collected to determine trends in the characteristics of HIV-positive patients. HIV-positive patients were more likely to be classified as ASA 1 or 2 than ASA 3 or 4 (odds ratio (OR) 2.1). HIV-positive patients with CD4 counts >200 cells/microl were more likely to be ASA 1 or 2 (OR 3.88). Of HIV-positive patients with CD4 counts <200 cells/microl, significantly more were classified as ASA 1 or 2 than ASA 3 or 4 (p < 0.0001). Three patients with CD4 counts <50 cells/microl were classified as ASA 1 or 2. The overall prevalence of HIV infection was 29.4%. Females, patients presenting for obstetric surgery, and younger age groups had higher disease prevalence rates. Patients aged 30 - 39 years (43.0%) had the highest prevalence of HIV infection; the lowest was in patients aged 60 years or older (7.7%). Routine clinical pre-operative assessment in patients from a population with a high HIV prevalence rate may result in asymptomatic, severe immune compromise being missed in a significant number of patients.